Twenty-first century science and technology endeavors, research and development innovations that solve problems for man-kind will increasingly be dominated by the ability to make structures and objects that have sizes with length scales approaching those of atoms and molecules having dimensions of a nano-meter or less. Nano-scale matter and objects exhibit unique behaviors, some of which have yet to be unraveled in addition to the known remarkable optical, thermal, electrical and mechanical properties. These open new vistas for many beneficial applications making them suitable for many applications. For example, sequencing, imaging, nano-lithography, manipulation, nano-scale self assembly, nanometer scale chemistry, and infinite other applications with benefit from nano-scale technology development.
It is envisioned and believed that being involved in the nano-size frontier of science, technology and innovation is a sure path to regional and national economic well being, and competitiveness. This is evidenced by the extraordinary investment activities by big and small countries, large and small private sector enterprises and nearly unparalleled entrepreneurial activities.
To advance in the nano-scale frontier science and technology requires access to and mastering the following:
Tools to produce nano-objects
Tools to measure sizes with sub-Angstrom precision
Substrates that have atomic smoothness with minimum contamination
Tools to see (image) nano-objects and manipulate them, grabbing, moving, gluing, etc.
Nano funnels/nozzles/probes for dispensing substances and stimuli
Tools to accurately measure all physical properties, thermal, electrical, optical,
Key parameters become smaller by 10 to 20 orders of magnitude of quantities accustomed to in the macro-world.
In the last 5 years the collective achievements of the best and brightest people around the world related to the above tools have grown at astonishing rates, delivering numerous discoveries, innovations, methods, products and tools.
One area that could tremendously benefit from nanotechnology is the -development of high-throughput DNA sequencers in the 1990's have helped launched the genomic revolution of the 21st century. Almost on a monthly basis, one research group or another is announcing the complete sequencing of a biologically important organism. This has allowed researchers to cross reference species, finding shared and/or similar genes, and allowing the knowledge of molecular biologists in all the various fields to come together in a meaningful way.
However, current techniques in DNA sequencing are far too tedious, tying up the valuable time of researchers. Even the fastest, most advanced DNA sequencers can at most process a few hundred thousand base pairs a day. The Human Genome Project took over 10 years to complete, indicating that current DNA sequencing technology still has a long way to go before it can be used as a diagnostic tool. Considering that there are about 3 billion DNA base pairs in the mammalian genome, and current sequencing technology is capable of sequencing about 2 million DNA base pairs per day, it would still take over 4 years to sequence the human genome.
Known nucleic acid sequencing methods are generally based on chemical reactions that yield multiple length DNA strands cleaved at specific bases. Alternatively, other known nucleic acid sequencing methods are based on enzymatic reactions that yield multiple length DNA strands terminated at specific bases. In either of these methods, the resulting DNA strands of differing length are then separated from each other and identified in strand length order. The chemical or enzymatic reactions, and the methods for separating and identifying the different length strands, usually involve repetitive procedures. Thus, there remains significant limitations on the speed of DNA sequencing using conventional technology.
Despite these limitations, an incredible collaborative heroic effort was undertaken for the Human Genome Project. It took many years and billions of dollars to obtain the sequence to the human genome. It would be highly desirable to provide a method and system that reduces the time and effort required would represent a highly significant advance in biotechnology. Indeed, frontier advances are required to increase the efficiency and speed of DNA sequencing if we are to expand the genome databases that presently exist to include a genome library including flora and fauna. Certain flowering plants have 100 times more base pairs than the human genome, so existing sequencing technology must be leaped for a new frontier of sequencing systems.
One particular type of sequencing method relies on passing strands of DNA through pores. For example, U.S. Pat. Nos. 5,795,782, 6,015,714, 6,267,872, 6,362,002 6,428,959 6,465,193 6,617,113, 6,627,067, 6,673,615, 6,746,594 6,870,361 describe various sequencing techniques and apparatus based on pores and flow of DNA fragments through pores. In general the prior art pores have thickness that cannot directly resolve with high spatial resolution without some other indirect deconvolution of the date resulting from changes in ionic conductivities. It further cannot be used for large DNA fragments. Further, it is very time consuming. In general, for an ultra fast DNA sequencing system, there are many limitations with pore based systems.
Therefore, it would be desirable to provide an improved system and method of analyzing extended objects such as linear polymers (including proteins, DNA and other biopolymers).